This application argues that progress in understanding the origins of racial and socioeconomic position (SEP) disparities has been impeded by several problems, the two most important of which are the problem of misclassification and the failure to adequately assess differences in stress exposure. In our view, information on the origins of health disparities can most effectively be pursued by an approach that avoids the typical classification error of counting disordered individuals as non-disordered because they do not exhibit the particular disease or disorder under investigation or have a nascent disorder that has not progressed enough to be clinically detectable. We suggest that such misclassification is likely to have obscured potentially modifiable factors that are centrally implicated in the documented elevation in health risk among African Americans and persons of low SEP, and argue that it can be avoided by a joining of biomarker methodologies for estimating physical health status and reliable estimates of the presence of psychiatric and substance use disorders/problems within a community-based population study. There is also evidence indicating that the failure of prior research to take account of a range of social stressors has significantly biased estimates of racial and SEP differences in exposure to stress and resulted in the systematic underestimation of the contributions of stress exposure to the occurrence of racial and SEP disparities in health. Among the unique aspects of the proposed research are: 1) the substantial avoidance of epidemiologic misclassification through the simultaneous consideration of one or more operationalizations of allostatic load and the assessment of cell aging, in combination with both clinical and subclinical assessments of psychiatric and substance use disorders/problems;2) estimation of stress exposure in terms of lifetime exposure to major and potential traumatic events, recent life events, chronic stressors, discrimination stress, and, among African Americans, stress arising from colorism and from uncertainty and/or ambiguity associated with covert discrimination;and 3) in the context provided by 1 and 2 above, to assess an exceptionally comprehensive array of hypothesized risk/protective factors including, through a subsequent grant application, gene-environment interactions. We will study a representative community-based sample of 1600 adults, ages 25 to 65 selected such that half are African American, half are female, and sufficient numbers of middle and upper SEP African Americans who do and do not live in segregated areas are included to allow at least substantial disentanglement of the effects of race, SEP, and segregation. The research proposed is aimed toward the identification of potentially modifiable social, contextual, and personal factors that contribute to racial and SEP health disparities. PUBLIC HEALTH RELEVANCE: The study addresses the social determinants of racial and socioeconomic position disparities in health. It employs biomarker data within a community epidemiologic design that promises to advance our understanding of potentially modifiable factors that underlie health disparities. It is likely to serve the needs of prevention science and hence has very significant public health implications.